title: Exclusive neuronal expression of SUCLA2 in the human brain.
abstract: SUCLA2 encodes the ATP-forming β subunit (A-SUCL-β) of succinyl-CoA ligase, an enzyme of the citric acid cycle. Mutations in SUCLA2 lead to a mitochondrial disorder manifesting as encephalomyopathy with dystonia, deafness and lesions in the basal ganglia. Despite the distinct brain pathology associated with SUCLA2 mutations, the precise localization of SUCLA2 protein has never been investigated. Here, we show that immunoreactivity of A-SUCL-β in surgical human cortical tissue samples was present exclusively in neurons, identified by their morphology and visualized by double labeling with a fluorescent Nissl dye. A-SUCL-β immunoreactivity co-localized >99 % with that of the d subunit of the mitochondrial F0-F1 ATP synthase. Specificity of the anti-A-SUCL-β antiserum was verified by the absence of labeling in fibroblasts from a patient with a complete deletion of SUCLA2. A-SUCL-β immunoreactivity was absent in glial cells, identified by antibodies directed against the glial markers GFAP and S100. Furthermore, in situ hybridization histochemistry demonstrated that SUCLA2 mRNA was present in Nissl-labeled neurons but not glial cells labeled with S100. Immunoreactivity of the GTP-forming β subunit (G-SUCL-β) encoded by SUCLG2, or in situ hybridization histochemistry for SUCLG2 mRNA could not be demonstrated in either neurons or astrocytes. Western blotting of post mortem brain samples revealed minor G-SUCL-β immunoreactivity that was, however, not upregulated in samples obtained from diabetic versus non-diabetic patients, as has been described for murine brain. Our work establishes that SUCLA2 is expressed exclusively in neurons in the human cerebral cortex.
authors.affiliation: Department of Anatomy, Histology and Embryology, Semmelweis University, Budapest, 1094, Hungary.
authors.forename: Arpád
authors.initials: A
authors.lastname: Dobolyi
authors.forename: Elsebet
authors.initials: E
authors.lastname: Ostergaard
authors.forename: Attila G
authors.initials: AG
authors.lastname: Bagó
authors.forename: Tamás
authors.initials: T
authors.lastname: Dóczi
authors.forename: Miklós
authors.initials: M
authors.lastname: Palkovits
authors.forename: Aniko
authors.initials: A
authors.lastname: Gál
authors.forename: Mária J
authors.initials: MJ
authors.lastname: Molnár
authors.forename: Vera
authors.initials: V
authors.lastname: Adam-Vizi
authors.forename: Christos
authors.initials: C
authors.lastname: Chinopoulos
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002540:Cerebral Cortex / Q000166:cytology* / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D013389:Succinate-CoA Ligases / Q000235:genetics / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D013389:Succinate-CoA Ligases; C518788:SUCLA2 protein, human